Even under optimal conditions, the utilization of food protein is inefficient. Optimal utilization of dietary protein is critical when quality food is scarce, in hypocaloric diets, in hepatic or renal deficiency, and in wasting chronic diseases. We want to understand how the interplay of anabolic and catabolic pathways minimizes the degradation of dietary amino acids and optimizes their storage as additional tissue proteins. Mice will be needle-fed dextrin and egg albumin. At different intervals afterwards, we will determine rates of protein synthesis and degradation in liver and extrahepatic tissues; concentrations of amino acids in plasma, liver and muscle; and production of urea. A comprehensive study of this nature has not been attempted in the past, because of technical limitations in estimating acute changes in protein turnover. We are now able to measure, in intact mice, instant rates of protein synthesis and degradation by relatively simple procedures developed in this laboratory, which permit us to generate data on a scale that had not been possible before. The experiments will explore the following interrelated mechanistic questions. (a) Is the efficient utilization of dietary amino acids limited by the capacity of the storage process? We will ask whether, under optimal conditions, increased urea production occurs only after maximum protein storage has been attained. (b) Can changes in protein turnover after a meal be entirely explained by the regulatory effects of insulin, glucagon and the amino acids themselves? We will modulate the participation of these factors by omitting egg albumin or dextrin, and we will attempt to interfere with the action of insulin and glucagon by the injection of antibodies to these hormones. (c) Does the liver play a unique role in protein storage (because of its high rate of protein turnover and its preferential access to absorbed amino acid in the portal blood)? This has added significance in parenteral nutrition, where the portal circulation is bypassed. We will correlate the production of urea with the hepatic concentration of amino acids, and ask how important are the changes in hepatic protein turnover when compared with other tissues.